The antiproliferative and competitive binding activities of several purifie species of human lymphoblastoid interferon alpha were compared to that of recombinant interferon alpha-2b on Daudi and AU937 cells. We found that the antiproliferative activity of the interferon species on each cell line has a broad range and that Daudi cells were more sensitive than AU937 cells. Th 50% inhibition of cell growth ranged from .003 ng/ml to greater than 10 ng/ml on Daudi cells and 1.2 ng/ml to greater than 100 ng/ml on AU937 cells Scatchard analyses demonstrated that the IFN-alpha 2b binding site number is greater on Daudi cells (12,700 binding sites/cell) than AU937 cells (3,300 binding sites/cell); however, their receptor affinities were similar Interestingly, there appears to be three species (n,o,p) which exhibit the highest antiproliferative activities on both cell lines but do not compete for the interferon alpha-2b binding site. These data suggest that there may be more than one receptor or multiple receptor components involved in the biological actions of these molecules. Studies are in progress to clone species o and to examine its receptor binding properties.